Nanomedicine-protein interactions: Understanding protein corona composition effects on nanomedicine cellular uptake

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From bench to clinic, a new drug candidate will face multiple roadblocks and challenges in its development. In oncology drug development, a balance has to be met between achieving tumour bioavailability and potential off-target organ toxicity- Nanomedicines have emerged as a promising solution to overcoming such challenges. When administered intravenously, a nanomedicine will be exposed to various biomolecules in blood. Some of these molecules will adsorb onto the nanomedicine surface, forming a 'corona', altering its chemical identity and biological fate. Hydrophobic nanomedicines have a shorter circulation half-life owing to a higher degree of opsonisation and subsequent clearance following recognition by the mononuclear phagocytic system. In a bid to improve circulation half-lives through reduced immune recognition clearance, stealthing with hydrophilic molecules such as PEG has been implemented as a standard approach in nanomedicine research.This studentship will investigate how nanoparticle physicochemical characteristics impact protein corona formation on nanoparticle surfaces, and the subsequent impact of protein corona formation on nanomedicine physicochemical characteristics and cellular interactions. Orthogonal particle metrology technologies will be applied to the characterization of nanomedicine physicochemical characteristics prior to and following protein corona treatment in plasma and cellular lysate. A limited number of studies to date have evaluated the impact of protein corona formation on nanomedicine physicochemical characteristics and subsequent biological fate. PLGA nanoparticles will be investigated as a model due to their extensive investigation as nanocarriers, established safety profile, maturity in the clinic, and significant lack of published reports on NP corona characterization. Findings from this work, in combination with parallel proteomics analysis offer the scope for developing predictive models of nanomedicine biological fate. This studentship will be the first of a series considering both dynamic and endpoint characterization of nanoparticle protein corona evolution over various timescales as a function of nanoparticle physicochemical attributes. Understanding protein corona composition has been recognized as a critical factor in deconvoluting the interplay between particle manufacture processes, critical quality attributes, and subsequent in vivo performance. Ultimately, predictive models of nanomedicine biological fate will create a step-change in the design and construction of novel nanomedicines with tunable protein corona profiles that can be exploited to improve drug biodistribution and therapeutic efficacy.